Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.
California NanoSystems Institute, University of California, Los Angeles, CA, 90095, USA.
Nat Commun. 2023 Feb 17;14(1):899. doi: 10.1038/s41467-023-36577-y.
Female mosquitoes inject saliva into vertebrate hosts during blood feeding. This process transmits mosquito-borne human pathogens that collectively cause ~1,000,000 deaths/year. Among the most abundant and conserved proteins secreted by female salivary glands is a high-molecular weight protein called salivary gland surface protein 1 (SGS1) that facilitates pathogen transmission, but its mechanism remains elusive. Here, we determine the native structure of SGS1 by the cryoID approach, showing that the 3364 amino-acid protein has a Tc toxin-like Rhs/YD shell, four receptor domains, and a set of C-terminal daisy-chained helices. These helices are partially shielded inside the Rhs/YD shell and poised to transform into predicted transmembrane helices. This transformation, and the numerous receptor domains on the surface of SGS1, are likely key in facilitating sporozoite/arbovirus invasion into the salivary glands and manipulating the host's immune response.
雌性蚊子在吸血时会向脊椎动物宿主注射唾液。这一过程会传播蚊媒传染病病原体，这些病原体每年共导致约 100 万人死亡。在雌性唾液腺分泌的最丰富和最保守的蛋白质中，有一种叫做唾液腺表面蛋白 1（SGS1）的高分子量蛋白质，它有助于病原体的传播，但它的机制仍不清楚。在这里，我们通过 cryoID 方法确定了 SGS1 的天然结构，表明这种 3364 个氨基酸的蛋白质具有 Tc 毒素样 Rhs/YD 壳、四个受体结构域和一组末端串联的卷曲螺旋。这些卷曲螺旋在 Rhs/YD 壳内部分被屏蔽，并准备转化为预测的跨膜螺旋。这种转变，以及 SGS1 表面的众多受体结构域，可能是促进孢子虫/虫媒病毒入侵唾液腺和操纵宿主免疫反应的关键。
